Tissue Resident CD8 Memory T Cell Responses in Cancer and Autoimmunity

Resident memory (T(RM)) cells are a distinct tissue-localized T cell lineage that is crucial for protective immunity in peripheral tissues. While a great deal of effort has focused on defining their role in immunity to infections, studies now reveal T(RM) cells as a vital component of the host immune response to cancer. Characterized by cell-surface molecules including CD103, CD69, and CD49a, T(RM)-like tumor-infiltrating lymphocytes (TILs) can be found in a wide range of human cancers, where they portend improved prognosis. Recent studies in mouse tumor models have shown that T(RM) cells are induced by cancer vaccines delivered in peripheral tissue sites, or by the depletion of regulatory T cells. Such tumor-specific T(RM) cells are recognized as both necessary and sufficient for long-lived protection against tumors in peripheral tissue locations. T(RM) responses against tumor/self-antigens can concurrently result in the development of pathogenic T(RM) responses to self, with a growing number of autoimmune diseases and inflammatory pathologies being attributed to T(RM) responses. This review will recount the path to discovering the importance of resident memory CD8 T cells as they pertain to cancer immunity. In addition to highlighting key studies that directly implicate T(RM) cells in anti-tumor immunity, we will highlight earlier work that implicitly suggested their importance. Informed by studies in infectious disease models, and instructed by a clear role for T(RM) cells in autoimmunity, we will discuss strategies for therapeutically promoting T(RM) responses in settings where they don't naturally occur.